What lab tests are recommended to monitor in patients with hepatitis C (HCV)?

Laboratory Monitoring for Hepatitis C Patients

For patients with chronic hepatitis C, laboratory monitoring requirements differ substantially based on treatment phase: pretreatment assessment requires comprehensive baseline testing including HCV RNA quantification, hepatic function panel, CBC, and fibrosis assessment; during treatment with modern direct-acting antivirals, most patients require minimal to no routine laboratory monitoring; and post-treatment assessment at 12 weeks requires HCV RNA and hepatic function panel to confirm sustained virologic response. 1

Pretreatment Assessment

Essential Baseline Laboratory Tests

• HCV RNA quantitative assay is mandatory before initiating antiviral treatment to confirm active infection and establish baseline viral load 1
• HCV genotyping/subgenotyping (1a/1b) should be performed prior to treatment to guide regimen selection 1
• Hepatic function panel including AST, ALT, bilirubin, albumin, and INR to assess baseline liver function 1
• Complete blood count (CBC) with platelet count to evaluate for thrombocytopenia suggestive of cirrhosis (platelet count <150,000/mm³ indicates possible cirrhosis) 1

Fibrosis Assessment

Calculate FIB-4 score using the formula: age (years) × AST (IU/L) / [platelet count (10⁹/L) × √ALT (IU/L)] 1

• FIB-4 score <1.45 has 90% negative predictive value for advanced fibrosis 1
• FIB-4 score >3.25 suggests cirrhosis with 65% positive predictive value and warrants additional evaluation 1

Additional fibrosis markers when cirrhosis is suspected:

• Transient elastography (FibroScan) with stiffness >12.5 kPa indicating cirrhosis 1
• AST/ALT ratio ≥1.0 is suggestive of cirrhosis, though not diagnostic alone 2, 3
• APRI score >2.0 suggests cirrhosis (calculated as [AST/upper limit of normal] × 100/platelet count) 1

Cirrhosis-Specific Testing

For patients with confirmed or suspected cirrhosis (FIB-4 >3.25 or other evidence):

• Calculate Child-Turcotte-Pugh (CTP) score using bilirubin, albumin, INR, ascites, and encephalopathy 1
• Liver ultrasound within prior 6 months to exclude hepatocellular carcinoma and subclinical ascites 1

Coinfection Screening

• HBsAg and anti-HBc testing is mandatory before initiating HCV treatment due to risk of HBV reactivation 4
• Test for HIV if risk factors present 1

On-Treatment Monitoring

Patients WITHOUT Cirrhosis

No routine laboratory monitoring is required for most patients without cirrhosis receiving modern direct-acting antiviral regimens 1

Patients WITH Cirrhosis

Optional blood tests may be ordered to monitor for rare hepatic decompensation, including bilirubin, AST, and ALT 1

• Patients should see a specialist if they develop worsening liver tests or jaundice 1

Special Populations Requiring Monitoring

Patients taking diabetes medications:

• Monitor for symptomatic hypoglycemia throughout treatment due to improved glucose metabolism with viral clearance 1

Patients taking warfarin:

• Monitor INR for subtherapeutic anticoagulation throughout treatment 1

Post-Treatment Assessment (SVR Confirmation)

At 12 Weeks or Later After Treatment Completion

Mandatory testing:

• Quantitative HCV RNA to confirm undetectable virus (virologic cure/SVR) 1
• Hepatic function panel (AST, ALT, bilirubin, albumin) to document transaminase normalization 1

Continue monitoring:

• Hypoglycemia monitoring for patients on diabetes medications 1
• INR monitoring for patients on warfarin 1

If transaminases remain elevated after achieving SVR:

• Assess for other causes of liver disease including NAFLD, alcohol, autoimmune hepatitis, or hemochromatosis 1

Acute Hepatitis C Monitoring

For patients with acute HCV infection:

• Regular laboratory monitoring every 4-8 weeks for 6-12 months including ALT and HCV RNA until ALT normalizes and HCV RNA becomes repeatedly undetectable 1
• Monitor for at least 12-16 weeks before initiating treatment to allow for spontaneous clearance, which occurs in 15-45% of acute infections 1
• Minimum HCV RNA assessment at 4-6 months after estimated infection onset to establish if chronic infection has occurred 1

Long-Term Follow-Up for Treatment Failures

For patients who do not achieve SVR:

• Assessment for disease progression every 6-12 months with hepatic function panel, CBC, and INR 1
• Annual HCV RNA testing for patients with ongoing risk factors (injection drug use, men who have sex with men engaging in unprotected sex) 1
• Test for HCV RNA whenever elevated ALT, AST, or bilirubin develops 1

Common Pitfalls to Avoid

Do not rely solely on AST/ALT ratio to diagnose cirrhosis - while an AST/ALT ratio ≥1 is suggestive of cirrhosis, it has only 77% positive predictive value and should not replace comprehensive fibrosis assessment 5

Do not assume normal ALT excludes active disease - AST may remain elevated when ALT normalizes, and some patients with significant fibrosis have persistently normal transaminases 6, 2

Do not over-monitor during treatment with modern DAAs - unlike older interferon-based regimens, current direct-acting antivirals have excellent safety profiles and most patients without cirrhosis require no routine laboratory monitoring during treatment 1